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ect of Hydrophobic Chain Length on the Stability and Guest Exchange Behavior of Shell-Sheddable Micelles Formed by Disul fi deLinked Diblock Copolymers
| Content Provider | Semantic Scholar |
|---|---|
| Author | Fan, Haiyan Li, Yixia Yang, Jinxian Ye, Xiaodong |
| Copyright Year | 2017 |
| Abstract | Reduction-responsive micelles hold enormous promise for application as drug carriers due to the fast drug release triggered by reducing conditions and high anticancer activity. However, the effect of hydrophobic chain length on the stability and guest exchange of reduction-responsive micelles, especially for the micelles formed by diblock copolymers containing single disulfide group, is not fully understood. Here, shell-sheddable micelles formed by a series of disulfide-linked copolymer poly(ethylene glycol)-bpoly(ε-caprolactone) (PEG−SS−PCL) containing the same chain length of PEG but different chain lengths of hydrophobic block PCL were prepared and well characterized. The influence of the chain length of hydrophobic PCL block on the stability and guest exchange of PEG−SS−PCL micelles was studied by the use of both dynamic laser light scattering (DLS) and fluorescence resonance energy transfer (FRET). The results show that longer PCL chains lead to a slower aggregation rate and guest exchange of micelles in the aqueous solutions containing 10 mM dithiothreitol (DTT). The cell uptake of the shell-sheddable PEG−SS−PCL micelles in vitro shows that the amount of internalization of dyes loaded in PEG−SS−PCL micelles increases with the chain length of hydrophobic PCL block investigated by flow cytometric analysis and confocal fluorescence microscopy. ■ INTRODUCTION It is well-known that self-assembly of amphiphilic block copolymers into polymeric micelles and vesicles can provide hydrophobic regions and/or hydrophilic cavities to encapsulate hydrophobic and/or hydrophilic drugs. These nanocarriers have received much attention over the last three decades due to an ability to prolong the circulation time of drugs in the blood and to accumulate in tumor tissues because of the enhanced permeability and retention (EPR) effect, which could also reduce side effects of anticancer drugs. Moreover, stimuliresponsive polymer micelles have been designed to trigger the release of drugs and enhance the therapeutic efficiency. In particular, micelles and nanogels formed from reductionresponsive polymer with monofunctional disulfide group or multifunctional disulfide groups have been shown to promote drug delivery in cancer cells, presumably due to the higher concentration of the reducing agent glutathione (GSH) in the cell interior (2−10 mM) than the extracellular environments (2−10 μM). For example, Zhong and co-workers reported that shell-sheddable micelles formed from block copolymers containing only one disulfide group between hydrophilic block and hydrophobic block released doxorubicin (DOX) much faster inside cells and showed a higher antitumor efficacy as compared to reduction insensitive micelles. They also found that dual-responsive biodegradable micelles and functionalized reduction-sensitive micelles exhibited superior tumor growth inhibition. Wang and co-workers reported that shell-detachable micelles assembled from a single disulfidelinked copolymer of poly(ε-caprolactone) and poly(ethyl ethylene phosphate) (PCL−SS−PEEP) displayed reductionresponsive release and faster intracellular DOX release. Oh and co-workers prepared a series of shell-sheddable micelles based on hydrophobic polylactide (PLA) block that exhibited enhanced release of encapsulated drugs from micelles. Although different reduction-sensitive micelles have been synthesized and characterized, the stability and guest exchange of these micelles are not well understood, in particular, for the micelles formed from diblock copolymers containing a single disulfide group. Until now, to the best of our knowledge, only a few studies have been done on the mechanism of the release of loaded compounds and drugs and guest exchange of the reduction-sensitive micelles. For example, Cheng et al. studied the stability of disulfide bonded poly(ethylene glycol)-(cysteine)4-poly(D,L-lactic acid) (PEG(Cys)4-PDLLA) in the bloodstream and they found that the reduction-sensitive micelles have a higher stability after systemic administration compared to the reduction-insensitive micelles using fluorescence resonance energy transfer (FRET) Received: June 23, 2017 Revised: August 29, 2017 Published: September 19, 2017 Article |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://staff.ustc.edu.cn/~xdye/60-Effect%20of%20hydrophobic%20chain%20length%20on%20the%20stability%20and%20guest%20exchange%20behavior-JPCB.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
